Supplementary Figures and Tables
Supplementary Table A.1: KLK8 expression in human brain single cells. Summarized are KLK8 expression data from several studies [1-4] and databases [5-7]. Shown are fractions of cells with KLK8 expression counts (in ‰) in neuronal as well as non-neuronal cells in several tissues and developmental stages.
Tissue Developmental
stage of donors
Number of nuclei
Fraction of cells with KLK8 counts (‰) Neuronal Non-neuronal Unclassified Excitatory Inhibitory
Allen Brain
Atlas Primary visual cortex Adult 8998 4 /8063 (0.50) 0/935
-Anterior Cingulate Cortex Adult 7283 - - -
-Middle temporal gyros Adult 15928 37/10525
(3.52) 8/4164 (1.92) 1/914 (1.09)
-GTEX Prefrontal cortex Adult 5932 - - -
-Hippocampus Adult 9036 0/3501 0/1061 0/3773 6/701 (8.56)
Linnarsson et al.
Ventral midbrain Embryo 1977 - - -
-Middle temporal gyrus
cortex Adult 2028 - - -
-Zhong et al. Prefrontal cortex Embryo
2309
- - -
-Darmanis et al. Temporal lobe Adult and fetal 466 5/122 (40.98) 1/206 (4.85) 0/138
PsychEncode Neocortex Fetal 115 1/40 (25) 0/28 0/47
-Frontal cortex Fetal 249 0/69 2/38 (52.63) 1/142 (7.04)
-Pallium Fetal 398 0/0 2/143 (13.98) 2/255 (7.84)
-Frontal cortex Adult 17093 0/8957 0/3721 0/4415
Supplementary Figure A.1: Single nucleotide polymorphisms (SNPs) associated with mental
disorders. A) In the currently largest genome-wide association studies (GWASs) no significant
association has been found between variants in the KLK8 locus and the mental disorders major
Schizophrenia (SZ), autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD)
[8-10]. However, three SNPs identified in a genotyping assay [11] show an association with BD and are
depicted here in the context of GWAS data. B) Shown are SNPs identified in GWASs in relation to the
UCSC genomic sequences of KLK8 splice variants in blue. Blue line: nominal significant threshold of
p < 0.05. Asterix indicate SNP located 3’ to KLK8.
Window Position Scale chr19:
CCDS
Human Feb. 2009 (GRCh37/hg19) chr19:51,499,264-51,508,516 (9,253 bp)
2 kb hg19
51,501,000 51,502,000 51,503,000 51,504,000 51,505,000 51,506,000 51,507,000 51,508,000 UCSC Genes (RefSeq, GenBank, CCDS, Rfam, tRNAs & Comparative Genomics)
Consensus CDS
NHGRI-EBI Catalog of Published Genome-Wide Association Studies
KLK8 KLK8 KLK8 KLK8
KLK8 KLK9 KLK9
KLK9
KLK9
rs10410942 rs34542531 rs74705037 rs74705037
rs1701946 rs1722550
MDD PGC + UKB BD PGC SZ PGC ASD iPSYCH ADHD iPSYCH
SNP OR P OR P OR P OR P OR P
rs1722550 0.985 0.065 0.998 0.868 1.005 0.653 0.984 0.343 0.988 0.449
rs1701946 0.986 0.074 1.009 0.498 1.002 0.889 0.977 0.163 0.986 0.391
rs1612902* 0.986 0.086 1.006 0.678 1.003 0.807 0.984 0.306 0.987 0.407
Window Position Scale chr19:
CCDS
Human Feb. 2009 (GRCh37/hg19) chr19:51,499,264-51,508,516 (9,253 bp)
2 kb hg19
51,501,000 51,502,000 51,503,000 51,504,000 51,505,000 51,506,000 51,507,000 51,508,000 UCSC Genes (RefSeq, GenBank, CCDS, Rfam, tRNAs & Comparative Genomics)
Consensus CDS
NHGRI-EBI Catalog of Published Genome-Wide Association Studies
KLK8 KLK8 KLK8 KLK8
KLK8 KLK9 KLK9
KLK9
KLK9
rs10410942 rs34542531 rs74705037 rs74705037
rs1701946
rs1722550
Window Position Scale chr19:
CCDS
Human Feb. 2009 (GRCh37/hg19) chr19:51,499,264-51,508,516 (9,253 bp)
2 kb hg19
51,501,000 51,502,000 51,503,000 51,504,000 51,505,000 51,506,000 51,507,000 51,508,000 UCSC Genes (RefSeq, GenBank, CCDS, Rfam, tRNAs & Comparative Genomics)
Consensus CDS
NHGRI-EBI Catalog of Published Genome-Wide Association Studies
KLK8 KLK8 KLK8 KLK8
KLK8 KLK9 KLK9
KLK9
KLK9
rs10410942 rs34542531 rs74705037 rs74705037
rs1701946 rs1722550
SZ_GWAS ADHD_GWAS ASD_GWAS
A
Supplementary Figure A.2: Flowchart describing the dataset search in MEDLINE and GEO. The last three steps in the flowchart describe the downstream workflow in R for identifying studies reporting KLK8 expression levels in mental disorders.
Supplementary Figure A.1
Title OR Description Or MeSH terms: "major depressive disorder" OR "unipolar
depression" OR "attention deficit hyperactivity disorder" OR "Alzheimer's disease" OR Alzheimer OR "bipolar disorder" OR anxiety OR "panic disorder" OR "dissociative identity disorder" OR "post traumatic stress disorder" OR "Parkinson's disease" OR "affective disorder" OR "mood disorder" OR "obsessive compulsive disorder" OR "Tourette syndrome" OR "attention deficit disorder"
AND Supplementary Fields: .csv OR .txt
920 studies
396 studies
112 studies
79 studies
Top Organism: Homo sapiens
Study type: Expression profiling (MPSS, RT-PCR, HTS), Methylation profiling (HTS)
Minimum number of samples: 10
Sorted by description, excluded brain tumor, neuroblastformation
and not released studies
8 studies 14 studies Datasets containing:
neuropsin expression
Neuropsin expression level: >0
Excluded raw data 26 studies
Sorted by relevance
Title OR Description Or MeSH terms: "major depressive disorder" OR "unipolar depression" OR "attention deficit hyperactivity disorder" OR "Alzheimer's disease" OR Alzheimer OR "bipolar disorder" OR anxiety OR "panic disorder" OR "dissociative identity disorder" OR "post traumatic stress disorder" OR "Parkinson's disease" OR "affective disorder" OR "mood disorder" OR "obsessive compulsive disorder" OR "Tourette syndrome" OR "attention deficit disorder"
AND Supplementary Fields: .csv OR .txt 920 studies
396 studies
112 studies
79 studies
Top Organism: Homo sapiens
Study type: Expression profiling
(MPSS, RT-PCR, HTS), Methylation profiling (HTS)
Minimum number of samples: 10
Sorted by description, excluded brain tumor, neuroblastformation
and not released studies
8 studies 14 studies Datasets containing:
neuropsin expression
Neuropsin expression level: >0
Excluded raw data 26 studies
Supplementary Figure A.3: KLK8 expression in mental disorders. Shown are KLK8 expression levels by age in several brain tissues and several mental disorder phenotypes as well as healthy controls from selected studies identified as described in Supplementary Figure A.2. In GSE80655 the transcriptome in 281 clinically annotated human post-mortem brain tissues has been measured. GSE104704 compared the genome-wide enrichment of H4K16ac in the lateral temporal lobe of AD individuals against both younger and elderly cognitively normal controls. GSE101521 conducted whole-transcriptome brain expression profiling in MDD and suicide. GSE112523 studied DNA methylation in neurons from post-mortem brains in SZ and BD and GSE102556 combined differential expression and gene co-expression network analyses to provide a comprehensive characterization of male and female transcriptional profiles associated with MDD across six brain regions. Screening of the data from those studies did not reveal significant differences in KLK8 expression levels between MDD, BD or SZ patients and healthy controls.
References:
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Supplementary Figure A.2 - continued
Female Male An C g D L PF C n Ac c
20 30 40 50 60 70 20 30 40 50 60 70
-0.4 0.0 0.4 -0.4 0.0 0.4 -0.4 0.0 0.4 Age n o rm a liz e d e x p re s s io n o f KL K8 Phenotype Bipolar Disorder Control Major Depression Schizophrenia GSE80655
lateral temporal lobe
50 60 70 80
0 1 2 3 Age n o rm a liz e d e x p re s s io n o f KL K8 Phenotype Aged, diseased Old Young GSE104704 Female Male fro n ta l co rt e x o f th e h u ma n b ra in
30 40 50 60 70 30 40 50 60 70 -0.50 -0.25 0.00 0.25 0.50 Age n o rm a liz e d e x p re s s io n o f KL K8 Phenotype Bipolar Disorder Control Schizophrenia GSE112523 Female Male d o rsa l la te ra l p re fro n ta l co rt e x (B ro d ma n n Ar e a 9 )
20 40 60 80 20 40 60 80 -0.4 0.0 0.4 0.8 Age n o rm a liz e d e x p re s s io n o f KL K8 GSE101521 Female Male An C g D L PF C n Ac c
20 30 40 50 60 70 20 30 40 50 60 70 -0.4 0.0 0.4 -0.4 0.0 0.4 -0.4 0.0 0.4 Age n o rm a liz e d e x p re s s io n o f KL K8 GSE80655
lateral temporal lobe
50 60 70 80
0 1 2 3 Age n o rm a liz e d e x p re s s io n o f KL K8 Phenotype
Aged, Alzheimer´s disease
Old Young GSE104704 Female Male d o rsa l l a te ra l p re fro n ta l co rt e x (Bro d ma n n Are a 9 )
20 40 60 80 20 40 60 80
-0.4 0.0 0.4 0.8 Age n o rm a liz e d e x p re s s io n o f KL K8 Phenotype Controls MDD non-suicides MDD suicides GSE101521 Female Male fro n ta l co rt e x o f th e h u ma n b ra in
30 40 50 60 70 30 40 50 60 70
-0.50 -0.25 0.00 0.25 0.50 Age n o rm a liz e d e x p re s s io n o f KL K8 Phenotype Bipolar Disorder Control Schizophrenia GSE112523
Supplementary Figure A.2
Female Male C g 2 5 a IN S d lPF C ; BA 8 /9 Nac O F C ; BA 1 1 Su b
20 40 60 80 20 40 60 80
-0.02 0.00 0.02 0.04 -0.02 0.00 0.02 0.04 -0.02 0.00 0.02 0.04 -0.020.00 0.02 0.04 -0.02 0.00 0.02 0.04 -0.02 0.00 0.02 0.04 Age n o rm a liz e d e x p re s s io n o f KL K8 Phenotype Control
Major depressive disorder GSE102556 Female Male C g 2 5 a IN S d lPF C ; BA 8 /9 Nac O F C ; BA 1 1 Su b
20 40 60 80 20 40 60 80
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